The manipulation of particles finds application in a wide range of fields, many of which are medical in nature. Particle manipulation, typically involving the application of a force to the particles which varies with the particle type (in accordance with their size, shape or some other characteristic), can allow particles to be sorted, separated and transported. In medical applications, particle manipulation can allow the sorting and separating of certain kinds of biological material (e.g. cells).
Dielectrophoresis (DEP) is a phenomenon that affects dielectric particles that are electrically polarizable. Dielectrophoresis occurs when these particles are subjected to a non-uniform electric field. The electric field has the effect of polarizing the particles, whereby their poles align along a direction governed by the field lines. Since the electric field is non-uniform, the poles may occupy points in the electric field in which the local field differs. In these circumstances, each pole experiences a different force from the local electric field. This leads to a non-zero net force on the particle.
The net force of the particle depends on a number of factors. Dielectric particles that are distinctly more or less polarizable than the surrounding liquid will experience stronger dielectrophoresis than dielectric particles that have similar polarizability to the liquid. The polarizability of a particle in turn may be determined by its size and shape, as well as the ability of charges contained in the particle to relocate within the particle.
Since the net force on each particle depends upon the difference in force exerted on each pole by the local field, the net force will tend to be larger in non-uniform electric fields that vary significantly in strength on a scale that is comparable to the size of the particles.
Because the dielectrophoretic force is proportional to the difference in electric field felt by the respective poles of a polarized particle, but not to the direction of the field, dielectrophoretic forces are present in static and in time varying electric fields. There are several distinct mechanisms by which a particle can become polarised, however, and these occur on different timescales.
Dipoles can be formed within the particle upon exposure to an electric field, resulting in a dipole moment aligned either parallel or anti-parallel to the applied field. The direction of the induced dipole (i.e. parallel or anti-parallel with the applied field) depends on the permittivity of the particle, relative to the surrounding liquid. At short timescales, in general, the particle is less polarisable than the surrounding liquid and hence the induced dipole will be aligned anti-parallel with the applied field and negative dielectrophoresis occurs. At longer timescales, the migration of surface charges dominates which generally leads to parallel dipole alignment and positive dielectrophoresis. This results in a frequency dependence of the direction of the dielectrophoretic force in time-varying electric fields in which, generally, positive DEP occurs at low frequencies and negative DEP occurs at high frequencies.
The Clausius-Mossotti factor describes the frequency dependence of dielectrophoresis. For a given particle, the sign of the Clausius-Mossotti factor changes at a characteristic frequency fcross-over. Typically, a particle exhibits positive dielectrophoresis (in which the particle moves toward regions of higher electric field gradient) below fcross-over, while negative dielectrophoresis (in which the particle moves toward regions of smaller electric field gradient) is exhibited above fcross-over. The effect of this cross-over from positive dielectrophoresis to negative dielectrophoresis (or vice versa), and the fact that different particle types typically have different values of fcross-over, can be used to distinguish between different kinds of particle, by appropriate selection of the frequency applied. Typical frequencies for particle manipulation by dielectrophoresis range from 10-100 kHz. It is appreciated that more complex particles such as cells may exhibit a more complex frequency dependence of the Clausius-Mossotti factor.
Since certain kinds of biological material such as blood cells, bacteria and viruses are polarizable, dielectrophoresis has been used to demonstrate manipulation of these particles (see, for example: Patel, S. et al. Microfluidic separation of live and dead yeast cells using reservoir-based dielectrophoresis, Biomicrofluidics 6 (2012); Crane, J. & Pohl, A. Journal of the Electrochemical Society 115, 584-586 (1968); Gagnon, Z. Cellular dielectrophoresis: applications to the characterisation, manipulation, separation and patterning of cells. Electrophoresis 32, 2466-2487 (2011); and Alshareef, M. et al. Separation of tumor cells dielectrophoresis-based microfluidic chip, Biomicrofluidics 7 (2013)). Electrodes are used to apply electric fields to liquids containing the particles (e.g. blood cells in plasma).
A problem associated with known DEP techniques for particle manipulation is that the electrodes used to apply the electric fields are generally incompatible with the presence of the samples which are to be manipulated (see, for example, Martinex-Duarte, R. Microfabrication technologies in dielectrophoresis applications—a review, Electrophoresis 33, 3110-3132 (2012)). For example, the particles can stick to and accumulate on the electrodes. Additionally, the liquid containing the particles can corrode the electrodes, which are typically metallic. The potentials applied across the electrodes to form the electric fields for dielectrophoresis may also lead to charge flow within the liquid, leading to shorting of the electrodes and also to Joule heating of the liquid itself.
Surface acoustic waves (SAWs) are acoustic waves that propagate close to the surface of an elastic material. For Rayleigh mode surface acoustic waves, displacement of the surface occurs in two directions. Firstly, there is a transverse displacement of the surface in a direction parallel to the surface normal. Secondly, there is a longitudinal displacement in the plane of the surface, parallel to the direction of propagation of the wave. Surface acoustic waves can be generated on the surface of a piezoelectric material using transducers placed on the surface.
Rayleigh mode surface acoustic waves can couple mechanically to liquids located on the surface. It has been shown that this effect can be used to manipulate liquids, including liquid mixing and droplet transport. Rayleigh mode surface acoustic waves can also be used to trap particles contained in the liquid (see, for example, C. D. Wood, S. D. Evans, J. E. Cunningham, R. O'Rorke, C. Walti, and A. G. Davies, “Alignment of particles in microfluidic systems using standing surface acoustic waves,” Applied Physics Letters, vol. 92, p. 0441404, 2008; C. D. Wood, J. E. Cunningham, R. O'Rorke, C. Walti, E. H. Linfield, A. G. Davies, and S. E. Evans, “Formation and manipulation of two-dimensional arrays of micron-scale particles in microfluidic systems by surface acoustic waves,” Applied Physics Letters, vol. 94, p. 054101, 2009; and R. D. O'Rorke, C. D. Wood, C. Wälti, S. D. Evans, A. G. Davies, and J. E. Cunningham, Acousto-microfluidics: Transporting microbubble and microparticle arrays in acoustic traps using surface acoustic waves J. Appl. Phys. 111, 094911 (2012)). The particle trapping is associated with the acoustic radiation force of the surface acoustic wave and the coupling between the Rayleigh mode surface acoustic wave and the particle is therefore mechanical. For example, it has been demonstrated that particles in a liquid on a surface in which a Rayleigh mode standing wave is present will accumulate toward the nodes or antinodes of the wave. Typical frequencies for particle trapping using Rayleigh mode surface acoustic waves range from 10-1,000 MHz.
Surface acoustic waves in piezoelectric materials are accompanied by local electric fields associated with the compression and expansion of the material by the wave. In the case of Rayleigh wave acoustic particle trapping, the manipulation is dominated by the mechanical wave with the effect of the electric field being negligible. Nevertheless, acoustic sensing techniques using SAWs employ a layer of metal (e.g. gold) on the surface of the piezoelectric material to prevent any coupling between the local electric field and the liquid or the particles contained therein.